tbuckley/cabot-search huggingface dataset:
Equity for under-served populations in lung cancer screening and treatment: Does mobile low-dose CT scanning lead to stage shift and diagnosis with potential cures at 4 years of follow-up?
Authors: Derek Raghavan, Darcy L. Doege, Kia Dungan, Mellisa S Wheeler, John Doty, Glenn Hickman, Kathryn Finch Mileham, Daniel R. Carrizosa
Journal: Journal of Clinical Oncology (2022)

8551 Background: Randomized trials proved that screening high-risk patients with LDCT of chest reduces lung cancer mortality. Under-served patients have missed this benefit in most studies through access issues. We showed that mobile LDCT improves access and now assess if this translates to equity of survival. Methods: We used two coaches with BodyTom © portable 32 slice low-dose CT scanners (Samsung) to screen uninsured and under-served heavy smokers for lung cancer (Oncologist, 2019). All films were reviewed by central panel using LUNG RADS technique. Protocol was approved by Advarra IRB. Medicare pts were excluded as insurance covered them for LDCT (causing negative bias for diagnosis as the elderly are at high risk). Results: We initially screened 1200 uninsured/under-insured subjects, mean age 61 years (range 55-64), with average pack year history of 47.8 (30-150); 61% male; 18% Black, 3% Hispanic/Latino; 78% rural. We found 97 pts with LUNG RADS 4 (high risk) lesions, 30 lung cancers (2.5%), including 18 at stage I-III treated with curative intent (60%); 5 incidental non-lung cancers (renal CA 2, head &amp; neck CA 1, pancreas CA 2); &gt; 50% with intercurrent cardiovascular disease and COPD seen on LDCT. Of eligible first-screen subjects, 51% attended 12 month repeat LDCT and 27% attended third LDCT. One pt (6%) treated with curative intent has relapsed to date (median follow up 2.5 years, with 25% beyond 3 years). An additional 288 screened pts revealed 9 lung cancers (5 stage I-III), confirming shift to early stage disease at diagnosis. Conclusions: Mobile LDCT yields higher screening rate for under-served pts than prior hallmark trials, with shift to early-stage detection of lung cancer, with sustained treatment-induced remissions beyond 4 years. This approach could be applied to improve national lung cancer survival in the under-served.
Systematic literature review and meta-analysis of clinical outcomes for previously-treated patients with advanced biliary tract cancer.
Authors: Mayur Amonkar, Andrew Frederickson, Torkia Grira, Grace Fox, Alexander Gozman, Usha Malhotra, William Malbecq, Fan Jin, Lauren Abderhalden
Journal: Journal of Clinical Oncology (2022)

e16143 Background: There is no standard chemotherapy available for previously treated, advanced (unresectable and/or metastatic) biliary tract cancer (BTC). This systematic literature review and meta-analysis were conducted to assess clinical outcomes of chemotherapies in this patient population. Methods: A systematic literature search was conducted through mid-2021 to identify relevant studies using Embase, MEDLINE, and Cochrane Central Register of Controlled trials (January 1, 2000–July 6, 2021) with additional searches of recent ASCO and ESMO conferences. Eligible study designs included randomized controlled trials, controlled clinical trials, and non-randomized clinical trials in patients (≥18 years age, Eastern Cooperative Oncology Group performance score 0 or 1) previously treated for advanced BTC and who had progressed on prior treatment (i.e., ≥2L). The outcomes of interest were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis among chemotherapies was performed to obtain a pooled estimate of the efficacy of standard treatments in BTC. The ORR meta-analysis was performed using the Freeman-Tukey double arcsine transformation. For time-to-event outcomes, published Kaplan-Meier curves for OS and PFS were digitized to create pseudo- individual patient data. A meta-analysis of the resulting pooled survival curves for OS and PFS were conducted following the methodology of Combescure et al. (2014). Results: In total, 39 unique studies were identified. Seventeen studies representing 22 unique therapy arms evaluating chemotherapies among 903 patients were included in the meta-analysis for ORR. The random effects pooled estimate for ORR was 6.6% (95% confidence interval [CI]: 4.1-9.7%). Median PFS (12 studies; 16 survival curves) was 3.1 months (95% CI: 2.5-3.8) with PFS rates at 6 and 12 months of 26.7% (95% CI: 19.8-36%) and 6.9% (95% CI: 4.1-11.7%), respectively. Median OS (15 studies; 19 survival curves) was 6.8 months (95% CI: 5.9-7.5) with OS rates at 6, 12, and 24 months of 55.3% (95% CI: 49.9-61.3%), 24.6% (95% CI: 20.0-30.2%), and 2.0% (95% CI: 1.1-3.8%), respectively. Conclusions: The limited efficacy of clinical outcomes for chemotherapies used in the treatment of advanced BTC suggest an opportunity to explore the potential clinical benefits of newer treatments (e.g., immunotherapies).
Disparities in delayed diagnosis, access to treatment, and treatment delays among Hispanic men with metastatic prostate cancer.
Authors: Nishwant Swami, Edward Christopher Dee, Brandon A Mahal
Journal: Journal of Clinical Oncology (2022)

6550 Background: Reporting racial/ethnic disparities in aggregate for Hispanics could obscure differences between subgroups given heterogeneity in social determinants of health. We sought to identify differences in delayed diagnosis, treatment status, and time to treatment among Hispanic subpopulations with metastatic prostate cancer. Methods: 2004-2017 data from the National Cancer Database (NCDB) was used to identify patients with prostate adenocarcinoma; patients were disaggregated by racial subgroup and Hispanic country-of-origin. Ordinal logistic regression defined adjusted odds ratios (aORs) with 95% CI of 1) presenting with Stage IV cancer, 2) receiving treatment, and 3) receiving delayed treatment (defined as treatment after 90 days). Sensitivity analysis was conducted for delayed treatment after 180 days. Results: Among 1,305,785 patients, Hispanic men had greater odds of presenting with stage IV prostate cancer compared with non-Hispanic White (NHW) men (aOR = 1.54 95% CI 1.50-1.58, p &lt; 0.001). All Hispanic racial subgroups were more likely to present with stage IV cancer with highest odds observed in Hispanic Black men (aOR 1.68 95% CI 1.46-1.93, p &lt; 0.001). Disparities were also observed in all country of origin subgroups, particularly for men of Mexican heritage (aOR 1.99 95% CI 1.86-2.12, p &lt; 0.001). Among men with metastatic disease, Hispanic men were less likely to receive treatment than NHW men (aOR 0.60 95% CI 0.53-0.67, p &lt; 0.001). Hispanic White patients were less likely to receive treatment compared with NHW men (Hispanic White aOR 0.58 95% CI 0.52-0.66, p &lt; 0.001). Upon disaggregation by country of origin, disparities persisted, particularly for men of Dominican heritage (aOR 0.52 95%CI 0.28-0.98 p = 0.044). Hispanic men were more likely to experience treatment delays when compared to NHW men (aOR 1.38 95%CI 1.26-1.52 p &lt; 0.001). All Hispanic racial subgroups experienced greater treatment delays, particularly Hispanic Black men (aOR 1.83 95%CI 1.22-2.75 p = 0.002). Men of Central or South American heritage had the greatest odds of treatment delays (aOR 1.48 95%CI 1.07-2.04 p = 0.018). Sensitivity analysis indicated consistent findings among Hispanic patients overall, Hispanic White patients, and patients of Mexican and Puerto Rican heritage. Conclusions: We found notable differences in stage IV cancer at presentation, treatment for metastatic disease, and delays in treatment when outcomes were stratified by racial subgroup and Hispanic country of origin. Future studies in Hispanic populations with disaggregated data are needed to characterize outcomes, study mediators of the observed variations, and develop targeted interventions.
Metastasis model of tumor deposit in colorectal cancer based on phylogenetic tree.
Authors: Qi Zhang, Tao Yu, Shiyao Zhang, Zhicheng Zhao, Jian Liu, Tong Liu, Gang Liu
Journal: Journal of Clinical Oncology (2022)

e15549 Background: Colorectal cancer(CRC) is often accompanied by tumor deposit(TD) metastasis, and TD status was only adressed in N1c staging in the TNM staging for CRC. However, TD states are very complex and diverse, including quantity, morphology, and biological behavior. The correlation between TD and clinical prognosis is far more complicated and needs to be discussed in more dimensions. At present, there are no reports of TD research from the genetic perspective. In this study, the phylogenetic tree approach was used to explore the metastasis pattern of TD, which might lay a foundation for better understanding its clinical significance. Methods: Poly-G was used to sequence multiple sections (n = 427) of normal tissue, primary tumor, TD, positive lymph node, and distant metastasis from 25 patients. Then, using the poly-G genotype to calculated the genetic distance between tumor and normal tissue and built the phylogenetic tree. We use root diversity score (RDS) index to reflect the intratumor heterogeneity of TDs. The evolutionary connection and clone origin between TD and paired samples was evaluated using a phylogenetic tree and RDS index. Results: A total of 427 samples from 25 patients were included, including 171 primary tumor (40.0%), 94 positive lymph nodes (22.0%), 110 tumor deposits (25.8%), 28 liver metastases (6.6%), 4 lung metastases (0.9%), and 20 peritoneal metastases (4.7%). There were 43 (39.1%) TDs with envelope and 67 (60.9%) TDs with irregular morphology, according to pathological morphology. A phylogenetic tree based on migration patterns and clonal origins was used to highlight the differences between envelope-TDs and irregular-TDs. The genetic distance between envelope-TDs and positive lymph nodes appeared to be less, and they were more likely to derive from the same source, but the genetic distance between irregular-TDs and positive lymph nodes was larger (P &lt; 0.05). Envelope-TDs had a sequential metastatic model that was consistent with positive lymph nodes. Unlike envelope-TDs, irregular-TDs tend to show more complex biological characteristics, such as nerve and vascular invasion, resulting in a more convoluted evolutionary relationship in the phylogenetic tree. Conclusions: Our findings provide genetic evidence for TD metastatic model, which has to be supported in future studies to ameliorate CRC TNM staging.
Real-world data comparing third and subsequent line regimens for treatment of metastatic triple-negative breast cancer in the United States.
Authors: Dvir Aran, Avital Klein-Brill, Michael Jordan Fisch, Shlomit Amar-Farkash
Journal: Journal of Clinical Oncology (2022)

e18765 Background: Eribulin is a commonly prescribed regimen for metastatic triple negative breast cancer (mTNBC) patients pre-treated with one or more chemotherapy regimens, although no clear survival benefit has been shown when compared to treatment of physician's choice (TPC) [1]. Here, using real-world oncology data we compare the impact of treatment with Eribulin vs. other common chemotherapies as third and subsequent lines of therapy on overall survival and post-treatment hospitalizations. Methods: We performed a retrospective cohort study of third and subsequent lines (3L+) treatment of patients with mTNBC between 1/2016 and 6/2021 using administrative claims data from the Anthem Cancer Care Quality Program. Real-world overall survival (rwOS) was defined as time from diagnosis to death. Real-world overall survival (rwOS) was defined as time from diagnosis to death. A Cox model with inverse probability of treatment weighting was used to adjust for age, ECOG, socioeconomic status, comorbidity, and liver and bone metastatic sites. Median rwOS was estimated using the weighted Kaplan-Meier method. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Results: We identified 210 (52%) individuals with mTNBC who received Eribulin (E) for 3L+, compared to 189 patients treated with other chemotherapies (O), which include carboplatin+gemcitabine, nab-paclitaxel, vinorelbine, paclitaxel, carboplatin and nab-paclitaxel+atezolizumab, ordered by frequency. We found no significant difference in any of the demographic and clinical features tested between the groups (Table). Median rwOS in the E group was 6.4 months, compared to 7.6 months in the O group (p-value = 0.4). In adjusted survival analyses to known confounders, E showed no significant difference in mortality (aHR: 1.09, 95% Confidence Interval [CI]: 0.87-1.37, p-value = 0.46). Furthermore, we found no significant difference in hospitalizations following the treatment between the E to the O group (36% vs. 39%, p-value = 0.6), length of stay (7 vs. 8 days, p-value = 0.8) and classes of associated severe adverse events. Conclusions: Our analysis of real-world oncology data aligns with National Institute for Health and Care Excellence (NICE) recent recommendation in showing no survival benefit or reduction in post-treatment adverse events when treating with Eribulin at 3L+ in metastatic TNBC patients.[Table: see text]
The analysis of BRAF fusions in Chinese patients with glioma.
Authors: Chuandong Cheng, Ying Ji, Tiantian Han, Didi Guo, Weijie Sun, Guanghua Lu, Fanfeng Bu
Journal: Journal of Clinical Oncology (2022)

e14031 Background: KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. KIAA1549-BRAF fusion has been considered to be a key variant of PA in WHO CNS5, however, fusions of BRAF with other partner genes leading to MAPK pathway activation, have been described rarely. Herein, we explore BRAF fusions profiles in Chinese glioma patients. Methods: Next generation sequencing of 131-gene profiling was performed to analyze BRAF fusions from 1955 Chinese brain tumor patients in 2019-2021. BRAF fusions were detected by following the standard operating procedure (SOP). We screened out the BRAF fusions, and calculated the mutation frequency and other rare BRAF gene fusions. Results: A total of 49 cases were detected with BRAF fusions, 36 cases were children (&lt; 18 years old), and 13 cases were adults, with a mean age of 13 years (0-57 years). Interestingly, 39(80%) of them were KIAA1549-BRAF fusions, the most common fusion is between KIAA1549 exon 16 and BRAF exon 9 (exon 16–exon 9) followed by (exon 15–exon 9) and (exon 16–exon 11). And the other ten were rare fusions, including DENND2A-BRAF, MRPS33(Intergenic)- BRAF, BCAS1- BRAF, TMEM176B-BRAF, RNF130-BRAF, RIN2-BRAF, GNAI1-BRAF, EXOC4-BRAF, TNK2-BRAF. Most retained BRAF exons 9–18 (7/10, 70%). There was a significant statistical difference in age that the non- KIAA1549-BRAF fusions group was higher than the KIAA1549-BRAF fusions group (25 vs. 10, p &lt; 0.005). Importantly, we identified new BRAF fusion variants resulting in RIN2-BRAF, EXOC4-BRAF, TNK2-BRAF and TMEM176B-BRAF rearrangements, which has not previously been reported in gliomas. Conclusions: We find new BRAF fusions in our 20% glioma patients. In addition, analysis of rare BRAF fusion may help guide diagnosis and develop potential targeted therapies of older PA.
SAMETA: An open-label, three-arm, multicenter, phase III study of savolitinib + durvalumab versus sunitinib and durvalumab monotherapy in patients with MET-driven, unresectable, locally advanced/metastatic papillary renal cell carcinoma (PRCC).
Authors: Toni K. Choueiri, Wanning Xu, Lynne Poole, Aino Telaranta-Keerie, Ryan Hartmaier, Thomas Powles
Journal: Journal of Clinical Oncology (2022)

TPS4601 Background: Papillary renal cell carcinoma (PRCC) is the most common subtype of non-clear cell RCC and accounts for 10–15% of RCCs. Approximately 80% of PRCC cases are MET-driven, characterized by genomic abnormalities resulting in dysregulation of the MET signaling pathway, making these abnormalities a potential therapeutic target for treatment. Savolitinib is an oral, potent and highly selective MET tyrosine-kinase inhibitor (TKI) demonstrating preliminary clinical activity in advanced solid tumors, including in MET-driven PRCC, defined as presence of any of the following molecular alterations, in the absence of co-occurring fumarate hydratase mutations: chromosome 7 gain, MET amplification, MET kinase domain variations, or hepatocyte growth factor amplification. In the Phase III SAVOIR study, in PRCC, savolitinib monotherapy showed encouraging efficacy vs the multi-targeted TKI, sunitinib. In addition, non-clinical studies suggest a possible synergistic anti-tumor effect of MET-inhibitors and programmed cell death-ligand (PD-L1) inhibitors, such as durvalumab; emerging data from the Phase I/II CALYPSO study investigating savolitinib plus durvalumab shows a notable efficacy signal in patients with MET-driven PRCC. Following these findings, the SAMETA study (NCT05043090) is designed to evaluate the efficacy and safety of savolitinib in combination with durvalumab vs sunitinib and durvalumab monotherapy in PRCC. Methods: In this open-label, three-arm, multi-center, Phase III study, adult patients with unresectable, MET-driven and locally advanced/metastatic PRCC are eligible. An estimated 200 patients (25 countries, 165 centers) will be randomized in a 2:1:1 ratio into three treatment arms (A–C) with stratification by International metastatic RCC database consortium risk group &amp; PD-L1 expression tumor status. Arm A: oral savolitinib 600 mg once daily (QD) plus intravenous (IV) durvalumab 1500 mg every 4 weeks (Q4W); Arm B: oral sunitinib 50 mg QD for 4 consecutive weeks, followed by a sunitinib-free interval of 2 weeks Q6W; Arm C: IV durvalumab 1500 mg Q4W. Study treatment continues until RECIST 1.1 disease progression or another discontinuation criterion is met. The primary endpoint is progression-free survival (by BICR; RECIST v1.1). Secondary endpoints include overall survival, objective response rate and duration of response. Safety (adverse events, vital signs, ECG, hematology and biochemistry parameters) will also be reported. The first patient was enrolled onto the study on 28 October 2021. Clinical trial information: NCT05043090.
Construction of a diagnostic model through the gene expression profile of the patients’ peripheral blood mononuclear cells and clinical characteristics for malignant lung nodules diagnosis.
Authors: Yi Cai, Zhuoqi Li
Journal: Journal of Clinical Oncology (2022)

e20527 Background: Low dose computed tomography (LDCT) is widely accepted for detecting early-stage lung cancer. However, it remains a great challenge for it to distinguish malignant lung tumors from benign lung nodules because of the high false positive rate. Therefore, a better non-invasive diagnostic tool is needed to improve the specificity. Methods: Two GEO datasets of expression profiling by array of peripheral blood mononuclear cells (PBMC) from patients with malignant lung nodules or non-malignant lung conditions, as well as relevant clinical information were downloaded and disposed. R package edgeR was applied to screen out the differentially expressed genes with |log2-fold change (FC)| ≥ 0.25 and p≤0.05. Logistic regression model was constructed based on GSE135304 dataset in order to find which factors contribute to the distinguishing of malignant lung nodules from non-malignant lung conditions, and this model was then validated in GSE108375 dataset. Results: 23 differentially expressed genes from the PBMC between patients with lung cancer and non-malignant lung conditions, and the patients’ lung nodule size and age were included in the diagnostic model through the logistic regression analysis. And in the training dataset GSE135304, the ROC curve shows the specificity of the model is 0.866 and sensitivity is 0.848, and the AUC value is 0.857. In the meantime, the specificity and sensitivity of the validation dataset GSE108375 are 0.865 and 0.893 respectively, and the AUC value comes to 0.879. Conclusions: This diagnostic model shows high sensitivity and specificity in both training group and validation group, so it may be a good tool for the mini-invasive diagnosis of malignant lung nodules.
Pre-existing interstitial lung abnormalities are independent risk factors for interstitial lung disease during durvalumab treatment after chemoradiotherapy in patients with locally advanced non–small lung cancer.
Authors: Wakako Daido, Takeshi Masuda, Nobuki Imano, Naoko Matsumoto, Hiroyasu Shoda, Kosuke Hamai, Yasuo Iwamoto, Yusuke Takayama, Shohei Mishima, Ken Masuda, Shigeo Kawase, Yoshikazu Awaya, Yoshifumi Nishimura, Naoki Shiota, Nobuhisa Ishikawa, Masahiro Yamasaki, Soichi Kitaguchi, Kazunori Fujitaka, Yasushi Nagata, Noboru Hattori
Journal: Journal of Clinical Oncology (2022)

8528 Background: The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by treatment of durvalumab, one of immune checkpoint inhibitors (ICI). Interstitial lung disease (ILD) is a clinically life-threatening toxicity of CRT or durvalumab. The patient-characteristics or dose-volume histogram parameters of radiotherapy have been reported to be the risk factors for radiation-induced pneumonitis. However, the risk factors for ILD during durvalumab therapy has not been established. Interstitial lung abnormalities (ILA) are generated by aging or smoking, and manifest as minor interstitial shadow on lung computed tomography (CT). We previously reported that ILA were risk factors for ICI-induced ILD in patients with advanced NSCLC, as well as non-lung cancer. Therefore, we investigated whether ILA could be risk factors for ILD during the durvalumab therapy. Methods: We retrospectively enrolled NSCLC patients who received durvalumab after CRT at 10 institutions from July 2018 to June 2021. Patient-information, patient-characteristics, dose-volume histogram parameters, chest CT findings, and laboratory data, were obtained. CT findings were examined using CT obtained after CRT and prior to durvalumab therapy. Results: A total of 153 patients were enrolled, and the prevalence of ILA was 37.8% (56 patients) before durvalumab treatment. Among the enrolled patients, 94 (63.5%) developed ILD during durvalumab therapy. The proportion of patients with grade 1, grade 2, or grade 3 ILD was observed to be 29.7% (44 patients), 25.7% (38 patients), and 8% (12 patients), respectively. Univariate logistic regression analysis revealed that higher age, higher dose volume histogram parameters (V5, V20, mean lung dose), and the presence of ILA were significant risk factors for grade 2 or more ILD. Multivariate logistic regression analysis showed that ILA, especially ground grass attenuation in ILA, was an independent risk factor for grade 2 or more ILD (odds ratio: 7.02, 95% CI: 2.95-16.69, p &lt; 0.0001). Conclusions: Pre-existing ILA are risk factors for ILD during durvalumab treatment after CRT. This observation is consistent with previously reported findings in patients with advanced lung cancer and non-lung cancer. Therefore, we should pay more attention to the development of grade 2 or more ILD during durvalumab treatment in patients with ILA.